AMBS research paper entitled Mesencephalic astrocyte-derived neurotrophic factor (MANF) secretion and cell surface binding are modulated by KDEL receptors:
In this research paper, the authors describe the process by which MANF's intracellular activity (autocrine) may be regulated through MANF binding to the canonical ER-specific retention receptors with the amino acid sequence 'KDEL', known as 'KDELRs' (KDEL Receptors). Researchers expressed, or blocked, a key amino acid sequence on the MANF molecule known as 'RTDL,' which is a highly-conserved amino acid sequence that was shown in this research paper to be required for retention of MANF in the ER, or for secretion of MANF out of the ER, with signal activation through the KDELRs. Further, the research paper goes on to suggest that certain KDELRs are resident on the cell surface membrane, and that MANF's extracellular activity (paracrine) is regulated, at least in part, via cell-surface KDELRs. Interestingly, the paper suggests that following ER stress, there is an increase in expression of KDELRs on the cell surface membrane, opening the possibility that MANF's paracrine activity may be more potent or broad in times of ER stress.
"This publication provides further insight into the biological profile of MANF and the proteins it interacts with in both an autocrine and paracrine fashion," said Gerald E. Commissiong, President & CEO of Amarantus. "As we learn more about its biological functions, we believe the Company is likely to find additional avenues to commercially exploit MANF's breakthrough biology, and bring new meaningful treatments to patients in a variety of indications, including orphan indications."
http://ih.advfn.com/p.php?pid=nmona&article=55867953
AMBS research paper entitled Mesencephalic
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